A study to elucidate the thermodynamic situation of transfer Ribonucleic Acids (tRNA) and aminoacyl-tRNA synthetases is proposed. One aspect of this study will focus on defining the energy and population distribution of the several conformations of tRNA in solution using differential scanning calorimetry and a recently developed mathematical deconvolution technique. Changes in these distribution functions upon interaction with specific ligands (e.g., Mg ions) will be investigated. Another part of this study will focus on defining the thermodynamics of interactions of specific ligands (amino acid, ATP, Mg ions, etc.) with aminoacyl-tRNA synthetase using calorimetric and spectroscopic techniques. The results of such studies will be correlated with kinetic data for the same system to provide further information about the molecular details of the activation of amino acids by the synthetase. Finally, thermodynamic and kinetic studies of the reaction between tRNA and its synthetase will be initiated in an effort to define the overall aminoacylation reaction. These sets of experimental information will be used to develop a complete thermodynamic description of the various interactions in which tRNA and its synthetase are involved. The goal will be to thermodynamically map the binding reactions and develop an understanding of the basis of specificity of the enzymatic reaction. Insofar as much of the obtained information about tRNA will be of a general nature, the results of this study should all be of importance in developing a better understanding of protein synthesis and other biological processes in which tRNA's are involved.